Objectives: Men with the metabolic syndrome (MetS) and type 2 diabetes (T2D) often have low testosterone levels. Elevating low testosterone levels may improve features of the MetS and glycemic control. In this analysis, we assessed effects of normalization of circulating testosterone on biomarkers of non-alcoholic fatty liver disease (NAFLD), and cardiovascular risk.

Design and methods: In a single-blind, 52-week clinical trial, 32 hypogonadal men with the MetS and newly diagnosed T2D were randomized to supervised diet and exercise (D&E) alone (n=16) or with additional transdermal testosterone gel (50 mg QD; n=16). The MetS was defined by the Adult Treatment Panel-III and the International Diabetes Federation. Hypogonadism was defined as a total testosterone ≤12.0 nmol/l. Endpoint were baseline adjusted change in biomarkers of NAFLD (GPT, GOT, g-GT, CRP) and cardiovascular risk (homocysteine, PAI-1, fibrinogen, Apo(a) and TG).

Results: Fifty-two weeks of T treatment resulted in a significantly larger improvement in all measured biomarkers of NAFLD in T treated patients as compared to supervised D&E alone. Levels of homocysteine, PAI-1, fibrinogen, Apo(a) and TG improved significantly in both treated groups, with PAI-1, fibrinogen and TG showing a significantly larger improvement in T treated patients as compared to supervised D&E alone.

Conclusions: Addition of testosterone to supervised D&E results in greater beneficial effects on biomarkers of NAFLD and cardiovascular risk. Our results invite to consider the significance of diagnosing and if warranted treating testosterone deficiency in men with diabetes type 2.